Products in primary use for wound closure are surgical sutures and staples. Sutures are recognized to provide adequate wound support. However, sutures cause additional trauma to the wound site (by reason of the need for the needle and suture to pass through tissue and the need to anesthetize the wound area via needle application) and are time-consuming to place, and, at skin level, can cause unattractive wound closure marks. Surgical staples have been developed to speed wound apposition and provide improved cosmetic results. However, surgical staples also impose additional wound trauma and require the use of ancillary and often expensive devices for positioning and applying the staples. Both sutures and staples are especially problematic in pediatric cases where the patient may have a strong fear response and refuse to cooperate with their placement, and in geriatric cases where the skin tissue is weaker and prone to tearing.
Alternatively, adhesives have been proposed as wound closure devices. One group of such adhesives is the monomeric forms of alpha-cyanoacrylates.
Reference is made, for example, to U.S. Pat. No. 5,328,687 to Leung et al; U.S. Pat. No. 3,527,841 to Wicker et al.; U.S. Pat. No. 3,722,599 to Robertson et al.; U.S. Pat. No. 3,995,641 to Kronenthal et al.; and U.S. Pat. No. 3,940,362 to Overhults, which disclose alpha-cyanoacrylates that are useful as surgical adhesives. All of the foregoing references are hereby incorporated by reference herein.
Typically, the cyanoacrylate surgical adhesive is applied to one or both surfaces of wounds or incisions, including the internal portions of the wound, with any excess adhesive being quickly removed from the bonding surfaces. Subsequently, the edges of the wound are held together until they adhere. See U.S. Pat. No. 3,559,652 to Coover, Jr. et al. Two coatings of adhesive may be applied to the wound surfaces. However, this method of application produces significant levels of histoxicity due to the surgical adhesive being trapped within the wound site.
An additional method of application of the cyanoacrylate surgical adhesive to wounds or incisions involves the formation of a bridge over the wound site. As described in U.S. Pat. No. 3,667,472 to Halpern, the incised tissues are held together and maintained in fixed relationship until a cyanoacrylate adhesive has been applied over the incision and allowed the necessary time to develop a bond. Excess adhesive is removed from the incision. However, the composition utilized in this process suffers from inadequate film strength and flexibility with high histotoxicity in wound sites.
These conventional methods of application of tissue adhesive generally do not specify a particular method that is preferable, nor is there any mention of placing more than minimal amounts of glue upon wounds. The conventional application techniques strive to reduce application of excessive amounts of tissue adhesive to the wound due to histoxicity.
A topical tissue adhesive commercially available is Histoacryl.RTM. available from B. Braun Melsungen AG of Germany. The manufacturer recommends use of this adhesive only for closure of minor skin wounds and not for internal use. Moreover the manufacturer recommends that the adhesive be used sparingly or in thin films because thick films do not increase the film strength and can lead to necrosis of surrounding tissue due to thermogenic reaction. Moreover, films formed from this adhesive are brittle, permitting severe dehiscence of wounds.
Plasticizers have been added to cyanoacrylate surgical adhesive compositions. See, for example, U.S. Pat. No. 3,759,264 to Coover, Jr. et al., U.S. Pat. No. 3,667,472 to Halpern, U.S. Pat. No. 3,559,652 to Banitt, the subject matter of which is incorporated herein by reference. However, the incorporation of plasticizers in such compositions has led to decreased film strength of the polymerized material. Accordingly, such compositions have been utilized only within the wound site and not over the wound site as a bridge.
Other additives have been employed in cyanoacrylate surgical adhesives for the purposes of modifying the cure rate and shelf life of the adhesives. For example, cyanoacrylate polymerization inhibitors or stabilizers including Lewis acids, such as sulfur dioxide, nitric oxide, boron trifluoride and other acidic substances, including hydroquinone monomethyl ether, hydroquinone, nitrohydroquinone, catechol and hydroquinone monoethyl ether. See, for example, U.S. Pat. No. 3,559,652 to Banitt, the subject matter of which is incorporated herein by reference. These compositions contain significant amounts of impurities and, thus, require substantial amounts of stabilizer to inhibit premature polymerization of the monomer.
Other adhesives include both plasticizers and stabilizing agents. For example, U.S. Pat. No. 5,480,935 to Greff et al. describes a tissue adhesive having a plasticizer and a polymerization inhibitor. However, the plasticizers disclosed therein (i.e., alkyl phthalates) are highly toxic and are not suitable for use in biocompatible medical adhesives.